A Study of Chemotherapy and Radiation Therapy Compared to Chemotherapy and Radiation Therapy Plus MEDI4736 (Durvalumab) Immunotherapy for Bladder Cancer Which Has Spread to the Lymph Nodes, INSPIRE Trial

Running, not enrolling · Phase 2

Conditions studied: Bladder Urothelial Carcinoma, Stage III Bladder Cancer AJCC v8

In brief

This phase II trial studies the benefit of adding an immunotherapy drug called MEDI4736 (durvalumab) to standard chemotherapy and radiation therapy in treating bladder cancer which has spread to the lymph nodes. Drugs used in standard chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with durvalumab may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving chemotherapy and radiation therapy with the addition of durvalumab may work better in helping tumors respond to treatment compared to chemotherapy and radiation therapy alone. Patients with limited regional lymph node involvement may benefit from attempt at bladder preservation, and use of immunotherapy and systemic chemotherapy.

Key facts

Study ID

NCT04216290

Run by

National Cancer Institute (NCI)

People needed

11

Starts

2021-03-17

Expected to finish

2027-05-19

Last updated by the study team

2026-05-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• STEP 1 (RANDOMIZATION) ELIGIBILITY CRITERIA:
• Patient must be >= 18 years of age.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of step 1 randomization.
• Patient must have histologically proven pure or mixed urothelial cancer of the bladder.
• NOTE: Small cell carcinoma is excluded, however other variant histologies are permitted provided a component of urothelial carcinoma is present.
• Patient must have documented node-positive and non-metastatic disease (any T, any N, M0). Node positivity must have been defined prior to receiving any systemic chemotherapy or induction chemotherapy.
• Node positivity can fall into either of the following categories and will be defined by imaging and/or biopsy:
• A lymph node >= 1.0 cm in short axis on imaging (i.e., CT or MRI or positron emission tomography [PET]/CT).
• A lymph node that is < 1 cm on imaging with either a biopsy confirming involvement with cancer or high suspicion of cancer.
• For patients who have received induction chemotherapy (any type of systemic chemotherapy) for node positive bladder cancer prior to enrollment, there must be no signs of disease progression (CR/partial response [PR] or stable disease [SD]) based on restaging imaging and cystoscopy, which consists of:
• CT chest, abdomen, and pelvis obtained after completion of induction chemotherapy and within 8 weeks prior to step 1 randomization.
• NOTE: MRI can be used instead of CT per treating physician discretion.
• Cystoscopic evaluation and attempt to perform maximal transurethral resection of bladder tumor (TURBT) performed by the participating urologist after completion of induction chemotherapy and within 12 weeks prior to step 1 randomization. If maximal TURBT is not possible for medical reasons, the enrollment must be discussed and approved with the study chair. Documentation of correspondences with the study chair must be kept on file.
• Patients who achieve CR upon cystoscopy per urologist with no visible tumor (i.e., no need for additional TURBT), are allowed to proceed in the study as adequate resection with no residual disease in bladder.
• For patients who have did not receive induction chemotherapy (any type of systemic chemotherapy) for node positive bladder cancer prior to enrollment, the following must be obtained:
• CT chest, abdomen, and pelvis completed within 8 weeks prior to step 1 randomization.
• NOTE: MRI can be used instead of CT per treating physician discretion.
• Cystoscopic evaluation and attempt to perform maximal TURBT performed by the participating urologist within 12 weeks prior to step 1 randomization. If maximal TURBT is not possible for medical reasons, the enrollment must be discussed and approved with the study chair. Documentation of correspondences with the study chair must be kept on file.
• For patients who may need repeat TURBT if their old TURBT has fallen out of window: If urologist determine no visible tumor (i.e., no need for additional resection) upon cystoscopy, they are allowed to proceed in the study as complete resection.
• Patient must not have received any previous radiation therapy to the pelvic area.
• Patient must agree to undergo CT simulation and treatment planning. If this is the first case registered at the site, then a pre-treatment radiation therapy (RT) review will be required and will take up to 3 business days. The patient cannot start radiation treatment prior to successful completion of this pre-treatment review. Therefore, careful planning is necessary to meet the deadline of starting radiation within 20 business days of step 1 randomization.
• Patient must not have presence of concomitant active upper tract tumors or urethra tumors. History of previously adequately treated non-muscle invasive bladder cancer (NMIBC) are eligible. Previously treated urothelial cancer or histological variant at any site outside of the urinary bladder are allowed, provided they have been Ta/T1/carcinoma in situ (CIS) and post treatment follow up imaging and endoscopic evaluation shows no evidence of disease.
• Patients with previous exposure to immune checkpoint inhibitor for non-muscle invasive disease are eligible. If given for NMIBC, the last dose must have been completed > 12 months prior to step 1 randomization.
• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
• All patients of childbearing potential must have a blood test or urine study within 14 days prior to step 1 randomization to rule out pregnancy.

Where it is running

• Alaska Breast Care and Surgery LLC — Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States
• Alaska Women's Cancer Care — Anchorage, Alaska, United States
• Anchorage Oncology Centre — Anchorage, Alaska, United States
• Katmai Oncology Group — Anchorage, Alaska, United States
• Providence Alaska Medical Center — Anchorage, Alaska, United States
• Mercy Hospital Fort Smith — Fort Smith, Arkansas, United States
• CHI Saint Vincent Cancer Center Hot Springs — Hot Springs, Arkansas, United States
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States
• VA Palo Alto Health Care System — Palo Alto, California, United States
• Penrose-Saint Francis Healthcare — Colorado Springs, Colorado, United States
• Rocky Mountain Cancer Centers-Penrose — Colorado Springs, Colorado, United States
• AdventHealth Porter — Denver, Colorado, United States
• Saint Anthony Hospital — Lakewood, Colorado, United States
• AdventHealth Littleton — Littleton, Colorado, United States
• Longmont United Hospital — Longmont, Colorado, United States
• AdventHealth Parker — Parker, Colorado, United States
• Saint Mary Corwin Medical Center — Pueblo, Colorado, United States
• Beebe South Coastal Health Campus — Millville, Delaware, United States
• Helen F Graham Cancer Center — Newark, Delaware, United States
• Medical Oncology Hematology Consultants PA — Newark, Delaware, United States
• Beebe Health Campus — Rehoboth Beach, Delaware, United States
• Sibley Memorial Hospital — Washington D.C., District of Columbia, United States
• Holy Cross Hospital — Fort Lauderdale, Florida, United States
• Anchorage Associates in Radiation Medicine — Anchorage, Alaska, United States

Full record on ClinicalTrials.gov

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